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The common acid related diseases of the upper GI tract could be considered as primarily due to the defect in barrier function either of the gastric mucosal or duodenal epithelium leading to the formation of gastric or duodenal ulcers. An attempt was made in this chapter to discuss the history of peptic ulcer disease in humans and methods for the production of acute gastric lesions and ulcers in experimental animals with the special attention focused to the contribution of Polish scientists and investigators into this field. Early surgical advances in the management of peptic ulcers were emphasized that were then subsequently replaced by pharmacological treatment (histamine H2-receptor antagonists, proton pump inhibitors) and considered as the major strategy against the acid disorders. This included the immense body of work performed by numerous group of investigators, including Polish researchers, to identify the effects of acid, bile salts, aspirin and other non-steroidal anti-inflammatory drugs (NSAID), stress, Helicobacter pylori (H. pylori) infection, prostaglandins (PG) and nitric oxide (NO) on the integrity of the gastrointestinal mucosa, which all were discussed in this chapter. The concept of major defensive mechanism in the stomach called "cytoprotection", originally proposed by Andre Robert is recalled in the relevance to the great contribution of polish scientist working at the Jagiellonian University in Cracow. These experimental studies gave a new insight into the mechanism of action of arachidonate cascade products such as PGs, tromboxanes and leukotrienes and had opened the new therapeutic avenues for the gastroprotective treatment of the acute gastric mucosal damage. Detailed studies revealed, however, that PG-induced cytoprotection offers a short-term protection against gastric lesions induced by corrosive agents but unfortunately this phenomenon gives a little, if any, impact to the process of ulcer healing. The experimental studies on healing of gastric ulcers that become supportive for the clinical trial in humans, performed also by polish pioneers and the effect of numerous growth factors (EGF, TGFalpha), NO inhibitors, cyclooxygenase- (COX)-1 and COX-2 inhibitors and new safer derivatives of NSAID releasing NO in protection and ulcer healing are discussed. Finally, the major discovery by Warren and Marshall of H. pylori that have been studied world-wide in experimental animals including also Polish investigators, allowed for the better insight to the pathological consequences of this germ infection in the gastric mucosa and helped to establish the anti-H. pylori eradication therapy.
In adult mammals cells generated in the subventricular zone (SVZ) migrate to olfactory bulbs (OB). Functional significance of this continuous neurogenesis is not clear. We injected opossums (Monodelphis domestica) for seven consecutive days with a 5HT1A agonist (8-OH-DPAT or buspirone), or its antagonist WAY100635. One hour after each of these injections bromodeoxyuridine (BrdU), a marker of dividing cells was also injected. Two months later, when newly generated neurons settled in the OB and matured the ability of these opossums to detect hidden food by olfactory cues was tested. Afterwards, numbers of BrdU-labeled cell nuclei in their OB were counted and a phenotype of labeled cells established. In all groups investigated the majority of new cells differentiated into neurons (55-76%) and a lower proportion into astroglia (6-12%). Numbers of BrdU-labeled cells differed depending on the applied treatment: both agonists of the 5HT1A receptor increased these numbers, while its antagonist decreased them. The increased number of new OB interneurons did not change the time required for finding all three food items and therefore did not improve the opossums' performance in this test of the olfactory perception. However, opossums that had the reduced number of new generated OB cells searched longer for each food item and in consequence took three times longer to find all three crickets, than did opossums from other groups. In conclusion, lower numbers of new neurons in the opossums OB correlated with their worse behavioral performance in a test based on olfactory perception.
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